Do the reaction under nitrogen, dry and degas everything with nitrogen (or maybe even argon) (especially solvents) before you do the reaction. The dimerisation is caused by oxidation of the thiolate by trace oxygen and water.

Actually the dimerization occurs on the pyrimidinone ring... But indeed, I also observed dimerization of the thiolate nucleophile (in case I was using it). I haven't tried such dry conditions, so this could cope with this problem too.

Anyway, the main problem still remains for the pyrimidinone ring...

Assuming you're trying to react the alkyl chloride on that pyrimidone with a thiolate, first deprotonate the thiol in degassed solvent under nitrogen, then add the pyrimidone to it dropwise (again in degassed solvent). Use a slight excess of thiolate as well.

Maybe it's worth to try to do it in the darkness?

Forming a soluble coordination complex of your molecule would prevent dimerization. Given the structure of your compound it seems probable that it would form a stable chelate with some tr. metal...

Problem being that many thiols have a large affinity for TMs, even a token amount of KCl or CaCl2 might do the trick, those are harder metals and probably better for the purpose.

Maybe dripping your chloromethylpyrimidinone to a solution of your nucleophile may do the trick. In this way you should not have formation of disulfide dimers, except maybe of your product, but that can be solved.

A good stoichiometric control is the best form to avoid undesired polymerizations, a good stirring, and a slow and controled adittion of the Chloromethylpyrimidinone diluted in the reaction solvent, could solve the problem, also try with a weak base and low temperature... may be under 0...good luck...

Ok, thanks to all for your advices and suggestions. I will test those various conditions and let you know if it is working or not.

Be carefull with the NH of you pyrimidinone core. Indeed, some reactions are known to "protect" the NH with alkyl group such as methyl group with potassium carbonate as base and MeI as nucleophile. So, in your case you have competitive reaction between the substitution of your chlorine and the NH of your pyrimidinone core ;-)

Exactly, but even when I try to "protect" by N-methylation with MeI (or even N-benzylation with benzylbromide), I get the unexpected Iodine/bromine analog of my thienopyrimidinone mixed with with the dimere...

Did you try to work with a methyl group in position 2 of the pyrimidinone (position between the two nitrogen). Then, you can or protect the NH with MeI (this should work in dry condition, e.g. ACN dry, potassium carbonate, MeI) followed by the bromination of the methyl group in position 2. Or, you can make chlorothienopyrimidine with POCl3 followed by the substitution with MeONa (you should have 4 methoxypyrimidine core), then bromination of the methyl in position 2 and deprotection of the methoxy (BBr3 or BF3.SMe2) to recover the free amide. In the case of introduction of methyl group as protecting group of NH (first idea) you will get a mixture of the methylated NH + the 4-methoxypyrimidinone derivative. I hope it will help you

O-trimethylsilylation of the pyrimidinone should do the trick.

I think you can try to use NaBH4 under nitrogen condition or argon